Head and Neck Adenoid Cystic Carcinoma: Focus on Outcomes of Intensity Modulated Proton Therapy

Abstract

In this study, we report cancer control outcomes and toxicity from intensity modulated proton therapy (IMPT) in patients treated for adenoid cystic carcinoma (ACC) of the head and neck. This study combines 2 prospective protocols evaluating IMPT in head and neck cancer. This analysis included patients with ACC, treated with IMPT in the adjuvant or definitive setting between December 2010 and June 2018. Patients with recurrent or metastatic disease were excluded. Locoregional control (LRC), disease free survival (DFS) and overall survival (OS) were estimated using the Kaplan Meier Method. Patterns of failure as well as toxicities were prospectively collected. Cox regression analysis was performed to determine prognostic factors. Toxicities were graded as per Common Terminology Criteria for Adverse Events version 4.01. 60 patients met the inclusion criteria for this analysis. Median follow-up was 2.9 years. Median age was 50 years (range 18-82) and 58% of patients were female. Primary treatment sites included: Peri-orbital (30%), oral cavity (17%), paranasal sinuses (17%), parotid gland (15%), nasopharynx (12%), oropharynx (7%), larynx (1 patient), and trachea (1 patient). As per AJCC 8th Ed, 22%, 18%, 17%, 44% of patients had T1, T2, T3 and T4 stage; only 1 patient had nodal involvement. Treatments involved surgery followed by chemo-IMPT, surgery followed by IMPT and definitive chemo-IMPT in 47%, 30%, and 23% of patients. Most frequent chemotherapy regimen included Cisplatin (63%) and Carboplatin (17%). Median dose was 64 Cobalt Gray Equivalent (range: 60-70 CGE). In patients treated with definitive chemo-IMPT, adjuvant chemo-IMPT and adjuvant RT alone, 3-year LRC was 83%, 92% and 90%, respectively (p=0.5); 3-year DFS was 44%, 87% and 90%, respectively (p=0.09); and 3-year OS was 80%, 85% and 100%, respectively (p=0.5). Acute toxicities included grade 3 dermatitis, mucositis, and dysphagia in 7%, 7%, and 1 patient; there was no grade 4 toxicity. There was a 7% rate of temporary feeding tubes and no permanent feeding tube. Chronic toxicities included 1 patient who developed optic neuropathy after treatment for a peri-orbital tumor. This is the largest cohort of head and neck ACC treated with IMPT. We report excellent cancer outcomes in patients treated with adjuvant IMPT +/- chemotherapy. In addition, Outcomes of patients treated with upfront chemo-IMPT were acceptable, despite typically high risk, more advanced disease. The acute and late toxicity profiles were highly favorable.